Other treatments: Azelaic acid (Azelex) is a dicarboxylic acid with bacteriostatic and keratolytic properties. The 20% cream formulation is approved for acne; a 15% gel is indicated only for rosacea. Azelaic acid may be particularly effective in the treatment of cases with postinflammatory hyperpigmentation or concomitant melasma.
The utility of sodium sulfacetamide (Klaron) lotion, which is used once or twice daily, may be attributed to its bacteriostatic properties. This agent is marketed for patients with dry or sensitive skin, although studies to support the utility of sodium sulfacetamide in this population are limited. Sodium sulfacetamide is contraindicated in patients with sulfa allergies.
Nonprescription products may be used as primary or adjunctive treatments. Most acne patients have used OTC products, such as benzoyl peroxide monotherapy (1%-10%) and salicylic acid (2%). Used twice daily in a multitude of formulations, these products are often a reasonable starting point for patients with mild acne. The utility of benzoyl peroxide rests in its ability to inhibit P. acnes through oxidation, although patients must realize that it will bleach fabrics. Salicylic acid is a weak keratolytic, with a small potential to evoke contact dermatitis. It is commercially available in numerous preparations, including washes, makeup, gels, lotions, and cleansers.
Systemic therapies
Oral antibiotics: In patients with mixed inflammatory and comedonal acne, topical and oral medications used in combination are often necessary to achieve maximal results. Topical retinoids in conjunction with topical or systemic antibiotics have demonstrated greater utility than antimicrobials alone in both comedonal and inflammatory lesions.19 Systemic antibiotics are considered first-line treatments for acne vulgaris. They decrease P. acnes colonization and also have intrinsic anti-inflammatory effects.20 Commonly prescribed oral antibiotics include erythromycin and tetracycline or its derivatives doxycycline and minocycline.
In patients with mixed inflammatory and comedonal acne, topical and oral medications used in combination are often necessary to achieve maximal results. Topical retinoids in conjunction with topical or systemic antibiotics have demonstrated greater utility than antimicrobials alone in both comedonal and inflammatory lesions. Systemic antibiotics are considered first-line treatments for acne vulgaris. They decrease colonization and also have intrinsic anti-inflammatory effects. Commonly prescribed oral antibiotics include erythromycin and tetracycline or its derivatives doxycycline and minocycline.
Erythromycin is a macrolide antibiotic that prevents the production of bacterial proteins. Although the therapeutic dose is usually 500 mg twice daily, a dose of 250 mg twice daily may be used initially and adjusted as necessary. The safety and tolerability profile of erythromycin are acceptable, with mild GI distress (the most common side effect) generally mitigated by the co-administration of food; the FDA classifies erythromycin as pregnancy category B. Unfortunately, P. acnes is quickly becoming resistant to erythromycin, which frequently makes this medication a second-line agent.
Tetracycline and its derivatives also prevent protein synthesis. Its direct anti-inflammatory properties play an important role in the therapeutic effect. The recommended starting dose is 500 mg twice daily. Tetracycline has the inconvenience of having to be taken on an empty stomach; patients should be instructed to take tetracycline one hour before or two hours after meals. Polyvalent cations (calcium, zinc, and iron) decrease systemic absorption. Tetracycline should not be used by pregnant women, or by patients younger than 9 years old because of the risk of tooth discoloration and inhibited skeletal growth. Moderate-to-severe phototoxicity (Figure 5) and GI intolerance may also limit the use of the tetracyclines. Intracranial hypertension can result from any medication in the tetracycline family, but this side effect may be more common if tetracyclines are administered in conjunction with isotretinoin.21
Doxycycline, a lipophilic tetracycline derivative, is commonly prescribed for moderate-to-severe acne vulgaris,
although photosensitivity may limit its usefulness. As with other tetracyclines, its action is primarily bacteriostatic, but bacteriocidal activity might occur by interference with bacterial protein synthesis. It is usually prescribed at a dose of 100 mg twice daily, although current studies are investigating the utility of smaller doses.
Minocycline is a potent acne medication but is typically reserved for patients who fail or cannot tolerate the aforementioned oral antibiotics. Rare, but serious, side effects are more common in patients taking minocycline than in those taking tetracycline or doxycycline,22 including hyperpigmentation, drug-induced lupus, autoimmune hepatitis, hypersensitivity reactions, and serum sicknesslike reactions. Vestibular toxicity is more common in patients taking minocycline than other tetracyclines. Minocycline is usually started at a dose of 100 mg twice daily.
Oral antibiotics must be taken for six to eight weeks before results are evident, and treatment should continue for a minimum of six months to prevent resistance.23 Once inflammation has resolved, oral antibiotics can be discontinued. During this transitional period, topical antibiotics may be used to prevent flaring, and topical retinoids should be continued. Some patients may require long-term oral antibiotic therapy to control their acne and prevent hyperpigmentation and scarring.
There is controversy regarding the possible decreased efficacy of oral contraceptives (OCs) in women taking systemic antibiotics. Although this concept is not supported by research, some OC package inserts warn of decreased effectiveness if the contraceptive is taken simultaneously with tetracyclines or ampicillin. Review of pharmacokinetic data demonstrated a reduction of contraceptive steroid hormones only with the concomitant use of rifampin. Nevertheless, it may be wise to inform patients using oral antibiotics of this risk and recommend the use of a second method of contraception during treatment with oral antibiotics. Women should also be warned about the possible increased incidence of vaginal yeast infections during treatment.
Isotretinoin: Isotretinoin (Accutane, Claravis, Amnesteem, Sotret) is a systemic vitamin A derivative used to treat severe nodulocystic and/or inflammatory acne. Isotretinoin has utility against all four pathogenic factors contributing to acne, and its mechanisms include induction of sebocyte atrophy, normalization of follicular keratinocytes, and reduction of P. acnes colonization. It also has direct anti-inflammatory effects. Isotretinoin is the only medication capable of providing a sustained remission of acne. Usually prescribed at dosages of 40-80 mg daily, the rate of absorption is increased with simultaneous ingestion of fatty foods. A total cumulative dose of 120–150 mg/kg has been shown to reduce the rate of relapse.24
The two most worrisome adverse effects of isotretinoin include severe birth defects and depression. Severe fetal abnormalities involving several systems will result from isotretinoin use during the gestational period. In an effort to educate patients regarding these possibilities, the manufacturer of Accutane (which has been withdrawn from the U.S. market) (Roche) developed the SMART program, which all prescribers of Accutane were required to join. Manufacturers of generic isotretinoin have similar programs. All these programs require two negative pregnancy tests prior to prescribing isotretinoin in reproductive-aged women and mandate that all patients use two forms of birth control throughout the treatment period and for one month afterward. Urine pregnancy tests are checked at each monthly visit. Other possible adverse effects of isotretinoin include hepatitis, hypertriglyceridemia, intracranial hypertension, arthralgia, myalgias, night blindness, and hyperostoses. Serum liver function tests and triglyceride levels are also monitored monthly during treatment.
The link between isotretinoin and depression is controversial. A meta-analysis published in 2000 reviewed the purported risk of depression, suicide, or psychiatric disorders in patients taking isotretinoin.25 In total, more than 7,500 patients on isotretinoin were reviewed from Canadian and United Kingdom databases, and there was no evidence that isotretinoin was associated with increased risk for depression, suicide, or other psychiatric disorders. Several case reports and case series, however, describe situations wherein depression occurred upon initiation and rechallenge with isotretinoin.